Radiological evaluation of newly diagnosed non-brainstem pediatric high-grade glioma in the HERBY phase II trial

Rodriguez, Daniel; Jones, Chris; Varlet, Pascale; Mackay, Alan; Warren, Daniel; Warmuth-Metz, Monika; S�nchez, Esther; Calmon, Raphael; Hargrave, Darren; Ca�ete, Adela; Massimino, Maura; Le Deley, Marie-C�cile; Saran, Frank; Rousseau, Raphael F; Zahlmann, Gudrun; Azizi, Amedeo A; Garcia, Josep; Vassal, Gilles; Grill, Jacques; Morgan, Paul S; Jaspan, Tim

Abstract

Purpose: The HERBY trial evaluated the benefit of the addition of the antiangiogenic agent Bevacizumab (BEV) to radiotherapy/temozolomide (RT/TMZ) in pediatric patients with newly diagnosed non-brainstem high-grade glioma (HGG). The work presented here aims to correlate imaging characteristics and outcome measures with pathologic and molecular data.

Experimental Design: Radiological, pathologic, and molecular data were correlated with trial clinical information to retrospectively re-evaluate event-free survival (EFS) and overall survival (OS).

Results: One-hundred thirteen patients were randomized to the RT/TMZ arm (n = 54) or the RT/TMZ+BEV (BEV arm; n = 59). The tumor arose in the cerebral hemispheres in 68 patients (Cerebral group) and a midline location in 45 cases (Midline group). Pathologic diagnosis was available in all cases and molecular data in 86 of 113. H3 K27M histone mutations were present in 23 of 32 Midline cases and H3 G34R/V mutations in 7 of 54 Cerebral cases. Total/near-total resection occurred in 44 of 68 (65%) Cerebral cases but in only 5 of 45 (11%) Midline cases (P < 0.05). Leptomeningeal metastases (27 cases, 13 with subependymal spread) at relapse were more frequent in Midline (17/45) than in Cerebral tumors (10/68, P < 0.05). Mean OS (14.1 months) and EFS (9.0 months) in Midline tumors were significantly lower than mean OS (20.7 months) and EFS (14.9 months) in Cerebral tumors (P < 0.05). Pseudoprogression occurred in 8 of 111 (6.2%) cases.

Conclusions: This study has shown that the poor outcome of midline tumors (compared with cerebral) may be related to (1) lesser surgical resection, (2) H3 K27M histone mutations, and (3) higher leptomeningeal dissemination.

Citation

Rodriguez, D., Jones, C., Varlet, P., Mackay, A., Warren, D., Warmuth-Metz, M., Sánchez, E., Calmon, R., Hargrave, D., Cañete, A., Massimino, M., Le Deley, M.-C., Saran, F., Rousseau, R. F., Zahlmann, G., Azizi, A. A., Garcia, J., Vassal, G., Grill, J., Morgan, P. S., & Jaspan, T. (2020). Radiological evaluation of newly diagnosed non-brainstem pediatric high-grade glioma in the HERBY phase II trial. Clinical Cancer Research, 26(8), 1856-1865. https://doi.org/10.1158/1078-0432.ccr-19-3154

• Journal Article Type: Article
• Acceptance Date: Dec 13, 2019
• Online Publication Date: Jan 10, 2020
• Publication Date: 2020-04
• Deposit Date: Jan 8, 2020
• Publicly Available Date: Jan 11, 2021
• Journal: Clinical Cancer Research
• Print ISSN: 1078-0432
• Electronic ISSN: 1557-3265
• Publisher: American Association for Cancer Research
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 8
• Pages: 1856-1865
• DOI: https://doi.org/10.1158/1078-0432.ccr-19-3154
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/3690623